Impact of Emulsifiers on GI Health

 As ultraprocessed food consumption has dramatically risen, so has concern that they — and the additives they contain ― contribute to gut diseases, including inflammatory bowel disease (IBD), gastrointestinal (GI) cancer, functional GI disorders, and irritable bowel syndrome.

One category of food additives, emulsifiers, is garnering attention due to preliminary evidence that they may harm GI and metabolic health, Kevin Whelan, PhD, professor of dietetics in the Department of Nutritional Sciences, Kings College London, London, England, told Medscape Medical News.

“Like other food additives — including artificial sweeteners, colors, microparticles, and nanoparticles — emulsifiers adversely affect the gut microbiome, intestinal permeability, and intestinal inflammation,” he said.

Although the evidence is largely derived from in vitro and animal models, with relatively few human interventional studies, Whelan said, the findings may have implications for public policy, the food industry, clinical practice, and research.

What Are Emulsifiers?

Emulsifiers are “detergent-like molecules” that help combine compounds that normally wouldn’t mix, like oil and water. They’re used to “maintain the texture and other physical properties of food, such as hydration, viscosity, structural integrity, heat and mold resistance, and mouth feel and taste,” Michael Camilleri, MD, DSc, professor and consultant, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.

These additives are commonly found in a wide variety of food products, including pastries, cakes, ice cream, desserts, chocolate, bread, margarine, nut butters, premade frosting and icings, and ready-to-eat meals.

Emulsifiers are common in processed food. Whelan and colleagues analyzed close to 13,000 food products in the UK supermarkets and found that emulsifiers were present in over half of them. A French study, found that emulsifiers are among the 10 most consumed food additives worldwide.

Moreover, use of these substances is growing dramatically. The size of the global emulsifier market is expected to jump from an estimated $8.92 billion in 2024 to approximately $17.28 billion by 2034, according to a report issued by Precedence Research.

How Emulsifiers Affect the GI Tract

A normal intestinal barrier serves a dual function: It allows the absorption of beneficial dietary components while preventing the passage of harmful ingested substances (eg, pathogens or toxins), Camilleri said.

It appears that emulsifiers contribute to gut diseases by damaging the intestinal barrier. “Emulsifiers exert a negative effect on tight junction proteins, decrease mucus thickness, decrease microbial diversity, and increase mucosal inflammation,” Camilleri said.

Because much of the understanding about the potential health impact of emulsifiers is based on animal models, it is unclear which substances are the most harmful, the exact mechanism by which they damage the intestinal barrier, and whether their effect on gut permeability is consistent, Camilleri noted. The impact may vary based on physiologic conditions and combinations with other foods and liquids, he added.

Nevertheless, it appears that two common emulsifiers — carboxymethylcellulose (CMC) and polysorbate 80 (also called Tween 80) — thin the mucus layer that protects the epithelial cells lining the intestines, alter proteins in the mucosa, and cause higher levels of bacterial translocation.

Some research demonstrates that CMC promotes bacterial overgrowth in the small intestine, while polysorbate 80 causes bacterial translocation across the epithelium, Whelan noted.

Emulsifiers also appear to trigger inflammatory pathways, specifically by activating transcription factor nuclear factor-kappa B, which induces the production of several pro-inflammatory genes, including those that encode cytokines such as TNF-alpha and interleukin-6. The resulting cascade of effects culminates in the development of mucosal inflammation.

In a study involving mice, exposure to CMC and polysorbate 80 caused pro-inflammatory changes in the microbiota and resulted in chronic colitis in mice that were engineered to be genetically susceptible to the condition. In wild-type mice, the impact of emulsifier exposure was metabolic dysregulation and low-grade chronic inflammation. These findings were validated in other studies using other models and/or other dietary emulsifiers, Whelan noted.

The mouse study also found that the degree of proximity between the microbiota in the lumen and the intestinal epithelium correlates with the extent of intestinal inflammation. This finding implies that “there could be a direct link between bacteria penetrating the mucus layer and the development of intestinal inflammation after emulsifier ingestion,” Whelan noted. “And, interestingly, the effects of emulsifier consumption were absent in germ-free conditions, further suggesting that emulsifier-induced changes in the intestinal microbiota are implicated in the inflammatory process.”

Some human studies also shed light on the negative impact emulsifiers may have on the GI tract.

Camilleri cited a human study that investigated the impact of high- and low-emulsifier diets (HED and LED, respectively) on intestinal permeability in healthy individuals in an unstressed state and an acutely stressed state, induced by intravenous injection of a stress-producing hormone. Researchers found that in the unstressed state, the HED actually improved barrier function; but under conditions of stress, it resulted in increased intestinal permeability, or leaky gut. By contrast, an LED was protective against the stress effect.

Another human study, cited by Whelan, used data collected from six 24-hour dietary recalls among 599 healthy adults over a 1-year period. Higher intake of emulsifiers was positively associated with glycoprotein acetyls — a serum inflammatory biomarker. And a pilot study of controlled feeding in healthy participants, also cited by Whelan, examined the impact of CMC consumption on gut microbiota and gut health. It found that CMC consumption moderately increased postprandial abdominal discomfort and adversely altered intestinal microbiota composition and the fecal metabolome.

Emulsifiers and IBD

The impact of emulsifiers on the gut of patients with Crohn’s disease (CD) isn’t clear, Whelan noted. In a recent trial, 24 patients with CD were randomly assigned to a healthy diet either high or low in emulsifiers for a 4-week period. Bowel wall thickness was reduced by 34% on HED and 15% on LED in those who completed the study. Quality of life and fatigue improved on both diets, with no statistically significant differences in outcomes between the diets.

“In the context of a healthy diet, the emulsifier content had no influence over disease activity over 4 weeks in patients with CD;” therefore, “recommendations to avoid emulsifiers in patients with active CD are not supported,” the researchers stated.

On the other hand, a 2017 study, found that the emulsifier carrageenan may have a negative impact on people with ulcerative colitis. For the study, 12 patients with ulcerative colitis in remission agreed to eliminate the emulsifier from their diets for up to 12 months. They were randomly assigned to take a daily capsule containing carrageenan or a placebo capsule throughout the study period. Three of the five taking carrageenan relapsed compared with none taking placebo. “Carrageenan intake contributed to earlier relapse in patients with ulcerative colitis in remission. Restriction of dietary carrageenan may benefit patients with ulcerative colitis,” the researchers concluded.

Whelan and colleagues conducted the ADDapt trial, which randomly assigned 154 patients with CD to receive 3 daily snacks without emulsifiers and grocery deliveries of emulsifier-free food for 8 weeks (intervention group) or similar groceries and snacks containing emulsifiers (control group). Both groups received dietary counseling, dietary resources, mobile apps to support shopping, and the supermarket deliveries represented 25% of their food. The emulsifiers consumed by the control group were carrageenan, CMC, and polysorbate 80.

The results showed that compared with patients in the control group, those in the intervention group were more than twice as likely to experience remission and more of them had a 50% reduction in fecal calprotectin — an objective measure of inflammation.

“We found that the low-emulsifier diet was effective in treating mild-to-moderately active Crohn’s disease,” Whelan commented. He and his colleagues will be conducting “ongoing mechanistic analyses” to examine the impact of the LED on gut microbiota and permeability, he said.

“It’s clear that more human studies are needed to focus on the impact of long-term emulsifier exposure in healthy individuals, as well as people with diseases characterized by a chronic intestinal inflammatory state,” Whelan added.

Take-Home Messages

Some people — especially those with GI conditions — may choose to reduce their emulsifier intake. Adherence to an LED has been shown to be feasible and potentially beneficial. It’s particularly doable when people receive counseling and support as Whelan and colleagues demonstrated in a 2020 study of patients with CD who succeeded in avoiding emulsifiers for 2 weeks. “The support participants received boosted their compliance,” Whelan commented.

Camilleri recommends “avoiding high-fat and highly processed foods, which damage the intestinal barrier, and eating foods that protect the barrier, such as the Mediterranean diet instead of the Western-type diet.” He noted that the Mediterranean dietary pattern emphasizes healthy unsaturated fats (eg, olive oil and nuts), plant-based choices (fruits, vegetables, and whole grains), and lean protein sources (eg, fish, legumes), all of which “favorably impact intestinal gut function and barrier.”

Based on currently available research, Whelan said, “it’s too soon to issue sweeping new public policies further restricting emulsifiers or give clinical guidance to people to avoid consuming food with emulsifiers altogether. But clinicians can certainly advise their patients to eat a less-processed diet, which will be beneficial to health in general and gut health in particular.”

Camilleri reported no relevant financial relationships. Whelan reported receiving research grants related to diet and gut health and disease from government agencies, including the Medical Research Council and National Institute of Health Research, charities, including Crohn’s & Colitis UK, The Helmsley Charitable Trust, Kenneth Rainin Foundation, and commercial funders, including the Almond Board of California, Danone, and the International Nut and Dried Fruit Council. He reported receiving speaker fees from Danone and is the holder of a joint patent to use volatile organic compounds as biomarkers in irritable bowel syndrome. 

https://www.medscape.com/viewarticle/impact-emulsifiers-gi-health-2025a1000yl7